Mucosal immune cell priming by intranasally delivered Haemophilus haemolyticus is associated with heterologous protection against influenza and nontypeable Haemophilus influenzae

Jack S Pepper; Caitlyn M Granland; Sharon L Clark; Ruth B Thornton; Josephine Bayliss; M Z Edison Foo; Wesley Billingham; Naomi Scott; Alma Fulurija; Deborah H Strickland; Selma P Wiertsema; Peter C Richmond; Elke J Seppanen; Lea-Ann S Kirkham; M Christian Tjiam

doi:10.3389/fimmu.2026.1855464

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Mucosal immune cell priming by intranasally delivered Haemophilus haemolyticus is associated with heterologous protection against influenza and nontypeable Haemophilus influenzae

Journal article

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Mucosal immune cell priming by intranasally delivered Haemophilus haemolyticus is associated with heterologous protection against influenza and nontypeable Haemophilus influenzae

Jack S Pepper, Caitlyn M Granland, Sharon L Clark, Ruth B Thornton, Josephine Bayliss, M Z Edison Foo, Wesley Billingham, Naomi Scott, Alma Fulurija, Deborah H Strickland, …

Frontiers in immunology, Vol.17, 1855464

2026

DOI: https://doi.org/10.3389/fimmu.2026.1855464

PMID: 42548815

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Abstract

Administration, Intranasal

Animals

Female

Haemophilus Infections - immunology

Haemophilus Infections - microbiology

Haemophilus Infections - prevention & control

Haemophilus influenzae - immunology

Haemophilus Vaccines - administration & dosage

Haemophilus Vaccines - immunology

Humans

Immunity, Mucosal

Influenza A virus - immunology

Mice

Orthomyxoviridae Infections - immunology

Orthomyxoviridae Infections - prevention & control

Introduction: Intranasal vaccines offer a needle-free strategy to enhance immunity to respiratory infections. We investigated the mechanism of action of a novel intranasal vaccine using the human respiratory commensal Haemophilus haemolyticus (Hh), previously shown to protect against nontypeable Haemophilus influenzae (NTHi) otitis media and accelerate clearance of influenza A virus (IAV). Methods: Mucosal and systemic cellular immune responses were assessed 2–144 hours after intranasal Hh treatment in mice, compared with placebo or the Toll-Like Receptor (TLR)2–6 agonist Pam2CSK4 using spectral flow cytometry. The impact of treatment on subsequent IAV and NTHi challenge was also evaluated. Results: Hh induced a distinct, tissue-specific immune signature with rapid recruitment of neutrophils and inflammatory monocytes to the lungs, peaking at 6 hours, earlier than Pam2CSK4. Hh also generated higher proportions of nasal CD103+CD4+ T cells within 48 hours, which further expanded following sequential IAV and NTHi infection. Discussion: These findings demonstrate that Hh primes mucosal immune responses to promote heterologous protection.

Details

Title: Mucosal immune cell priming by intranasally delivered Haemophilus haemolyticus is associated with heterologous protection against influenza and nontypeable Haemophilus influenzae
Authors/Creators: Jack S Pepper - Infectious Diseases Institute
Caitlyn M Granland - Infectious Diseases Institute
Sharon L Clark - Infectious Diseases Institute
Ruth B Thornton - The University of Western Australia
Josephine Bayliss - Infectious Diseases Institute
M Z Edison Foo - Infectious Diseases Institute
Wesley Billingham - Biostatistics, The Kids Research Institute Australia, Perth, WA, Australia
Naomi Scott - Infectious Diseases Institute
Alma Fulurija - The University of Western Australia
Deborah H Strickland - The Kids Research Institute Australia
Selma P Wiertsema - Biocon (Switzerland)
Peter C Richmond - The University of Western Australia
Elke J Seppanen - The University of Western Australia
Lea-Ann S Kirkham - Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
M Christian Tjiam - The University of Western Australia
Publication Details: Frontiers in immunology, Vol.17, 1855464
Publisher: Frontiers Media S.A.
Identifiers: 991005909767907891
Murdoch Affiliation: School of Medical, Molecular and Forensic Sciences
Language: English
Resource Type: Journal article

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